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Changes in cyclooxygenase metabolities in experimental periodontitis in Macaca mulatta
Author(s) -
Offenbacher S.,
Odle B. M.,
Braswell L. D.,
Johnson H. G.,
Hall C. M.,
McClure H.,
Orkin J. L.,
Strobert E. A.,
Green M. D.
Publication year - 1989
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.1989.tb00859.x
Subject(s) - flurbiprofen , cyclooxygenase , medicine , thromboxane , periodontitis , endocrinology , prostaglandin , chemistry , pharmacology , platelet , enzyme , biochemistry
The four principal metabolites of cyclooxygenase (CO) were examined during the progression of experimental periodontitis in the rhesus monkey Macaca mulalla. Thirty‐two monkeys were divided in four disease‐matched groups. Three groups were treated with flurbiprofen a potent CO inhibitor, at either 0.027, 0.27 or 7.1 mg/kg/day delivered systemically by a subcutaneously‐implanted osmotic mini‐pump. We have previously described the findings indicating that flurbiprofen treatment significantly retarded clinical attachment loss (ALOSS), redness and radiographic bone loss (BLOSS). This investigation focuses on the changes in CO metabolites which occur during disease progression of ligature‐induced periodontitis and on the dose‐response relationship of flurbiprofen, as it relates to disease inhibition and the suppression of ARA metabolites within the crevicular fluid (CF). In untreated animals there was a statistically significant 3‐fold increase in CF levels of prostaglandin E 2 (PGE 2 ) and thromboxane B 2 (TxB 2 ) at 3 months, as compared to baseline, which positively correlated with increases in redness, bleeding, ALOSS and BLOSS. CF‐PGE 2 and TxB 2 levels reached a 6‐fold peak at 6 months and returned to baseline by 12 months. Flurbiprofen (Fb) prevented the 3‐month rise in TxB 2 , but did not affect the increase in PGE 2 . At 6 months, Fb administration caused a dosedependent inhibition of both PGE 2 and TxB 2 . Probit analysis of the doseresponse data revealed that the concentration of Fb which caused a 50% inhibition of CF‐TxB 2 level (the IC 50 value for TxB 2 synthesis) was approximately two logs lower than the IC 50 value for PGE 2 synthesis, i.e. TxA 2 ‐IC 50 = 0.013 vs . PGE 2 ‐IC 50 1.35 mg flurbiprofen/kg/d. The slopes of the PGE 2 , and TxB 2 inhibition curves were identical, consistent with a similar mechanism or singular enzyme for the site of action of Fb inhibition of CO activity. However, the kinetics and sensitivity of Fb inhibition were significantly different for the CO activity responsible for TxB 2 and PGE 2 synthesis, perhaps due to different compartmentalization of CO within different cell types.